A high expression of MTERF3 correlates with tumor progression and predicts poor outcomes in patients with brain glioma

Int J Clin Exp Pathol. 2019 May 1;12(5):1909-1920. eCollection 2019.

Abstract

Mitochondrial transcription termination factor 3 (MTERF3) is a negative regulator of mitochondrial transcription. MTERF3 is overexpressed in liver cancer, pancreatic cancer, lung cancer, and breast cancer. However, whether MTERF3 is up-regulated in brain glioma is still unclear. The aim of this study was to investigate the expression and clinicopathological significance of MTERF3 in brain glioma and to analyze its potential prognostic value in brain glioma. Immunohistochemistry, Western blot, and a semi-quantitative RT-PCR were performed to analyze the protein and mRNA expression levels of MTERF3 in 28 human brain glioma tissues and 10 noncancerous brain tissues. The expression data of MTERF3 and its clinical information in brain glioma were downloaded from the TCGA dataset using R 2.15.3 software. The relationship between the expression of MTERF3 and its clinicopathological characteristics and its prognostic value was analyzed. A Cox regression model was used for a multivariate analysis of the factors affecting the prognosis of brain glioma. The immunohistochemistry results showed that the MTERF3 protein is located in the cytoplasm, and the positive expression rate of the MTERF3 protein in brain glioma tissues is 64.29%. We found that the positive expression rate of the MTERF3 protein in high-grade glioma tissues (81.25%) is higher than it is in low-grade glioma tissues (41.67%). The expression levels of the MTERF3 mRNA and protein in brain glioma tissues are significantly higher than they are in the noncancerous brain tissues. Moreover, the expression of MTERF3 is significantly correlated with age, tumor type, and pathological classification (P<0.05). A Kaplan-Meier analysis showed that a high expression level of MTERF3 mRNA indicated a poor prognosis (log rank P<0.01). Furthermore, a multivariate Cox regression analysis showed that age and tumor type were independent prognostic factors for brain glioma patients. A GEPIA analysis suggested that the expression levels of MTERF3 are positively correlated with the TFAM, TFB1M, TFB2M, MTERF1, MTERF2, TEFM, and MFN1 genes, but negatively correlated with the PINK1 gene. The expression level of MTERF3 had no correlation with the MTERF4 gene. In conclusion, these data indicate that the expression of MTERF3 in glioma tissue samples can be used as a prognostic factor for patients with glioma and that a high MTERF3 expression correlates with a poor prognosis in glioma patients.

Keywords: MTERF3; TCGA dataset; brain glioma; immunohistochemistry; prognosis.